2026-04-17T12:01:29Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/118682025-10-24T10:37:13Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Wu, Jen-Hao
author
Pennesi, Edoardo
author
Bautista, F.
author
Garrett, May
author
Fukuhara, Kei Fukuhara
author
Brivio, Erica
author
Diaz de Heredia, Cristina
2025-10-24T10:37:13Z
2025-10-24T10:37:13Z
2024-08-26T07:04:20Z2024-08-26T07:04:20Z2024-07
http://hdl.handle.net/11351/11868
Population pharmacokinetics; Inotuzumab ozogamicin; Acute lymphoblastic leukemiaFarmacocinètica poblacional; Inotuzumab ozogamicina; Leucèmia limfoblàstica agudaFarmacocinética poblacional; Inotuzumab ozogamicina; Leucemia linfoblástica agudaBackground and Objective
Inotuzumab ozogamicin is an antibody-drug conjugate approved for treating relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in adults. Pediatric pharmacokinetic data of inotuzumab ozogamicin are lacking. This study is the first to examine the population pharmacokinetics of inotuzumab ozogamicin in pediatric patients with relapsed/refractory BCP-ALL.
Methods
From 531 adult patients with B-cell non-Hodgkin’s lymphoma, 234 adult patients with BCP-ALL, and 53 pediatric patients with BCP-ALL, 8924 inotuzumab ozogamicin serum concentrations were analyzed using non-linear mixed-effects modeling. A published adult inotuzumab ozogamicin population-pharmacokinetic model, a two-compartment model with linear and time-dependent clearance, was adapted to describe the pediatric data.
Results
Modifications in this analysis, compared to the published adult model, included: (i) re-estimating pharmacokinetic parameters and covariate effects; (ii) modifying covariate representation; and (iii) introducing relevant pediatric covariate effects (age on the decay coefficient of time-dependent clearance and ALL effect (disease type and/or different bioanalytical analysis methods) on initial values of time-dependent clearance). For patients with relapsed/refractory BCP-ALL, increasing age was associated with a decreasing decay coefficient of time-dependent clearance, reflecting that the target-mediated drug clearance declines more rapidly in children. In pediatric BCP-ALL, the median [interquartile range] cumulative area under the concentration–time curve was significantly higher among responders (n = 42) versus non-responders (n = 10) at the end of the first cycle (26.1 [18.9–35.0] vs 10.1 [9.19–16.1], × 103 ng*h/mL, p < 0.001). From simulations performed at the recommended pediatric phase II dose, inotuzumab ozogamicin exposure reached a similar level as observed in responding pediatric trial participants.
Conclusions
The pharmacokinetic profile of inotuzumab ozogamicin in pediatric patients with relapsed/refractory BCP-ALL was well described in this study. No dose adjustment is required clinically for pediatric patients with BCP-ALL based on the simulated inotuzumab ozogamicin exposure at the recommended pediatric phase II dose, promising efficacy and acceptable tolerability.ITCC-059 was sponsored by Erasmus MC and financed by Pfizer.
Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess
Infants
Leucèmia limfoblàstica - Tractament
Medicaments antineoplàstics - Ús terapèutic
Càncer - Recaiguda
DISEASES::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma::Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological
Other subheadings::Other subheadings::/therapeutic use
NAMED GROUPS::Persons::Age Groups::Child
DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence
ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades linfáticas::trastornos linfoproliferativos::leucemia linfoide::leucemia-linfoma linfoblástico de células precursoras::leucemia-linfoma linfoblástico de células B precursoras
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica
Otros calificadores::Otros calificadores::/uso terapéutico
DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::niño
ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::recurrencia
Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion